Novel tricyclic alcohols, novel uses of tricyclic alcohols and processes for preparing same

ABSTRACT

WHEREIN EACH OF R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 is selected from the group consisting of hydrogen and methyl; wherein the dashed line is a carbon-carbon single bond or a carbon-carbon double bond; wherein R1 is limited to hydrogen when (i) the dashed line is a carbon-carbon single bond; (ii) R2, R3, R4, R6, R7, R8, R9 and R10 is hydrogen and (iii) R5 is hydrogen or methyl and wherein when the dashed line is a carbon-carbon single bond, one of R3 or R4 is hydrogen; and processes for preparing the above-mentioned compounds and in addition compounds having similar structures, that is, when the dashed line is either a carbon-carbon single bond or a carbon-carbon double bond; R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are each the same or different and each represents hydrogen and wherein when R3 or R4 is hydrogen the dashed line represents a carbon-carbon single bond and when R3 and R4 are both methyl, the dashed line represents a carbon-carbon double bond, involving first intimately admixing a methyl substituted cyclohexadienone having the structure: The ketone may either be immediately cyclized using an alkali metal such as sodium, potassium or lithium in the case of X being halogen, or when X is OH, the ketone is first halogenated with a halogenating agent to first form a compound having the structure:     WHEREIN X can be either hydroxyl, bromo or chloro thereby forming a diene compound having the structure:   AND THEN HYDROGENATING THE DIENE COMPOUND WITH HYDROGEN IN THE PRESENCE OF A HYDROGENATION CATALYST THEREBY PRODUCING A KETONE HAVING THE STRUCTURE:   WHEREIN Y is bromo or chloro and subsequently the halogenated compound may then be cyclized using a cyclizing agent.   D R A W I N G   WITH AN ACETYLENIC COMPOUND HAVING THE STRUCTURE:   D R A W I N G Processes and compositions for altering the flavor and/or aroma of consumable products including foods, tobacco and perfumes utilizing as the essential ingredient at least one organic tricyclic alcohol having the formula:

United States Patent [1 1 Light et a1.

[451 Sept. 23, 1975 NOVEL TRICYCLIC ALCOHOLS, NOVEL USES OF TRICYCLICALCOHOLS AND PROCESSES FOR PREPARING SAME [75] Inventors: Kenneth K.Light, Asbury Park,

N.J.', Edward J. Shuster, Brooklyn, N.Y.; Joaquin F. Vinals, Red Bank;Manfred Hugo Vock, Locust, both of NJ.

[73] Assignee: International Flavors & Fragrances Inc., New York, N.Y.

22 Filed: Jan. 28, 1974 21 Appl. No.: 436,848

[52] U.S. Cl. 260/617 F; 131/17 R; 252/89; 252/132; 252/173; 252/522;260/586 C;

OTHER PUBLICATlONS Mirrington et al., J. Org. Chem, Vol. 37, No. 18(1972), pp. 2871-2877.

Corey et al., Science, Vol. 178-192.

Danishevsky et al., Chemical Communication, (1968). PP. 1287-1288.

Umarini et al., P & E.O.R., Sept./Oct. 1969, p. 307. Dobler et al.,Proc. Chem. Soc., Dec. 1963, p. 383.

Primary Examiner-Joseph E. Evans Attorney, Agent, or Firm-Arthur L.Liberman, Esq.; Harold Haidt, Esq.

[57] ABSTRACT Processes and compositions for altering the flavor and/oraroma of consumable products including foods, tobacco and perfumesutilizing as the essential ingredicut at least one organic tricyclicalcohol having the formula:

HO R1 wherein each of R R R R R R R R R and R is selected from the groupconsisting of hydrogen and methyl; wherein the dashed line is acarboncarbon single bond or a carbon-carbon double bond; wherein R islimited to hydrogen when (i) the dashed line is a carbon-carbon singlebond; (ii) R R R R R R R and R is hydrogen and (iii) R is hydrogen ormethyl and wherein when the dashed line is a carbon-carbon single bond,one of R or R is hydrogen; and processes for preparing theabove-mentioned compounds and in addition compounds having similarstructures, that is, when the dashed line is either a carbon-carbonsingle bond or a carbon-carbon double bond; R R R R R R R-,, Rg, R and Rare each the same or different and each represents hydrogen and whereinwhen R or R is hydrogen the dashed line represents a carbon-carbonsingle bond and when R, and R are both methyl, the dashed linerepresents a carbon-carbon double bond.

2 Claims, No Drawings NOVEL TRICYCLlC ALCOHOLS, NOVEL USES OF TRICYCLICALCOHOLS AND PROCESSES FOR PREPARING SAME BACKGROUND or THE INVENTIONThe compounds are prepared by first intimately admixing a methylsubstituted cyclohexadienone having the structure:

wherein X can be either hydroxyl; bromo =or chloro thereby formingadiene compound having the structure:

and then hydrogenating". the en'e cor'npound with hydrogen inthe'presence of-athydrogenation catalyst thereby producing a ketonehaving the structure:

The keton'e may either be immediately cyclized using an alkali metalsuch as sodium, potassium or lithium in the case of X being halogen, orwhen X is OH, the ketone is first halogenated with a halogenating agentto first form a compound having the structure:

wherein Y is bromo or chloro and subsequently the halogenated compoundmay then be cyclized using a cyclizing agent.

Materials which can provide atchouli-like, amber and woody fragrancenotes are known in the art of perfumery.-Many of-the natural materialswhich provide such fragrances and contribute desired nuances toperfumery compositions are high in cost, vary in quality from one batchto another and/or are generally subject to the usual variations ofnatural products.

There is accordingly a continuing effort to find syn thetic materialswhich will replace the essential fragrance notes provided by naturalessential oils or compositions thereof. Unfortunately, many of thesesynthetic materials either have the desired nuances only to a relativelysmall degree or else contribute undesirable or unwanted odor to thecompositions. The search'for materials which can provide a'more refinedpatchoulilike fragrance has been difficult and relatively costly in ifHC CH CH2 tions and perfumed articles. The compounds disclosed are:

a. Octahydro-l ,4,9,9-tetramethyl-4,7- methanoazulen-3(2H)-one havingthe structure:

b. Octahydro-l ,4,9,9-tetramethyl-4,7- methanoazulen-2(3H)-one havingthe structure:

Octahydro-l ,4,9,9-tetramethyl-4,7-

methanoazulen-8(7H)-one having the structure:

Umarani et al., Sept/Oct. 1969, P. & E.O.R., 307 discloses two compoundsrelevant to the instant case: isopatchoulinol having the structure:

and patchouli alcohol having the structure:

In addition, artificial flavoring agents for foodstuffs have receivedincreasing attention in recent years. in many years, such food flavoringagents have been preferred over natural flavoring agents at least inpart due to their diminished cost and their reproducible flavorqualities. For example.- natural food flavoring agents such as extracts,concentrates and the like are often subject to wide variations due tochanges in the quality, type and treatment of the raw materials. Suchvariations can be reflected in the end product and result in unfavorableflavor characteristics in said end product. Additionally, the presenceof the natural product in the ultimate food may be undesirable becauseof increase tendency to spoil. This is particularly troublesome in foodand food uses where such products as dips, soups, chips, sausages,gravies and the like are apt to be stored prior to use.

The fundamental problem in creating artificial flavor agents is that theartificial flavor to be achieved be as natural as possible. Thisgenerally proves to be a difficult task since the mechanism for flavordevelopment in many foods is not completely known. This is notica ble inproducts having woody-balsamic, fresh walnutkernel and walnut-skinflavor characteristics.

Reproduction of woody-balsamic, fresh walnutkernel and walnut-skinflavor and aroma has been the subject of long and continuing searches bythose engaged in a production of foodstuffs and beverages. The severeshortage of food in many parts of the world has given rise to thedevelopment of previously unused sources of protein which areunpalatable. Accordingly, the need has arisen for the use of flavoringmaterials which will make such sources of protein palatable to humansensory organs.

Even more desirable is a product that can serve to substitute fordifflcult-to-obtain natural perfumery oils and at the same timesubstitute for natural flavoring ingredients in both foodstuffs as wellas in tobacco.

Mirrington and Schmalzl 37 J.Org.Chem.N0. 18, 1972, pages 2871-2877discloses the isolation of patchouli alcohol having the structure:

An article by Corey and Wipke entitled Computer- Assisted Design ofComplex Organic Syntheses" appearing in 166 Science 178'( 1969) setsforth, interalia, the sequence of reactions leading to compounds havingthe structures:

: OH I ---OH One of these reaction sequences involves performing thereactions:

However, syntheses of methyl homologues and double compoundisorners andan analogues patchouli alcohol and dihydropatchouli alcohol have not yetbeen disclosed in the prior art. Indeed, economic syntheses of patchoulialcohol itself do not appear to be given in the literature. I

Danishevsky and Dumas 1968 Chemical Communication, Pages 1287-1288discloses the synthesis of racemic patchouli alcohol and epi patchoulialcohol having the structure:

by means of cyclization of a compound having the structure:

The use of perfumery of the compound having the structure:

("dehydro-norpatchoulinol") is disclosed in the following patents:

1. Belgium Pat. No. 788,301 issued Mar. 1, i973 2. GermanOffenlegungschrift No. 2,242,913 published Mar. 8, 1973 3.- Dutchpublished Application 72/11760 published Mar. 5, 1973 A product of thereduction of this compound is also disclosed (norpatchoulinol). Thisproduct has the structure: 7

The compounds of our invention have properties considered to beunobvious, unexpected and advantageous with respect to the properties ofthe above-mentioned prior art compounds.

THE INVENTION It has now been determined that certain tricyclic alcoholsare capable of imparting a variety of flavors and fragrances to variousconsumable materials. Briefly, our invention contemplates altering theflavors and/or fragrances of such consumable materials by adding theretoa small but effective amount of at least one tricyclic alcohol havingthe structure:

wherein each of R R R R R R R R R and R is selected from the groupconsisting of hydrogen and methyl; wherein the dashed line is acarbon-carbon single bond or a carbon-carbon double bond; wherein R, islimited to hydrogen when (i) the dashed line is a carbon-carbon single;(ii) R R R R R R R and R10 is hydrogen and (iii) R is hydrogen or methyland wherein when the dashed line is a carbon-carbon single bond. one ofR or R is hydrogen and flavoring and fragrance compositions containingsuch tricyclic alcohols. The invention also contemplates novel processesfor producing such compounds as well as other compounds having thegeneric structure set forth above wherein the dashed line is acarboncarbon single bond or a carbon-carbon double bond and each of R RR R R R R R R and R is the same or different and each representshydrogen or methyl with the proviso that the dashed line is acarbon-carbon single bond when one of R or R is hydrogen.

The tricyclic alcohols produced according to the process of ourinvention, a number of which are used in practicing the part of ourinvention concerning flavoring and fragrance compositions are actuallyracemic mixtures rather than individual steroisomers, such as the caseconcerning isomers of patchouli alcohol which are so obtained frompatchouli oil.

Specific examples of novel products or synthesis which have been foundto be useful for the purposes of our invention are as follows:

A. The compound having the structure:

This compound has a warm patchouli-like fragrance aroma and awoody-balsamic, walnut-kernel and walnut-skin like taste in foodflavors.

This compound has a warm patchouli fragrance and a woody-balsamic,walnut-kernel and walnut-skin like taste.

The tricyclic alcohols prepared according to the present invention canbe obtained by means of two closely related reaction sequences; setforth below:

The first route comprises first intimately admixing amethylcyclohexadienone having the structure:

The reaction temperature may be from -220C with a temperature range ofl00-200C being preferred. The reaction is preferably carried out atsuper- "atmospheric pressures and'pressures in the range of producthaving the structure:

wherein X may beeither hydroxyl, bromo and chloro thereby forming adiene compound having the struc ture:

In this reaction, it is best to proceed at a temperature in the range of200-260C withthe most preferred temperature being 220C. The reaction maybe carried out in the presence of an inert solvent such as benzene,hexane or cyclohexane (or any other inert solvent) or the reaction maybe carried out in the absence of solvent. Although, either theacetylenic compound or'the cyclohexadienone may be used'in excess, it ispreferred to use equimolar quantities of each reactant.

The above-mentioned diene compound is then hydrogenated with hydrogen'inthe presence of'a catalyst such as palladium, platinum, nickel or othersuitable hydrogenation catalyst. I

l-l50 atmospheres are suitable. Preferred pressures range from 5-l50atmospheres.

The hydrogenation reaction gives rise to a ketone but it is noteworthythat the compound produced is one where the dashed line isa-c'arbon-carbon single bond if one of R or R is hydrogen and thecompound is primarily one where the dashed line is a carbon-carbondouble'bond if R and R are both methyl.

When X is" halogen, the ketone thus produced may then'be immediatelycyclized by treating same with an alkali metal selected from the groupconsisting of sodium, potassium or lithium.'The cyclization may becarried out'in diethyl ether, tetrahydrofuran or benzeneIThe reaction'temperature preferred is the reflux temperature of the reaction mass atatmospheric pressure'and is a function of the solvent used. Thus, forexample, when using t'etrahydrofuran'solvent, the cyclization reactiontemperature is approximately 65C.1The reaction can be carried out attemperatures ranging from 0C up to 100C. For the cyclization, the moleratio of ketone to metal is preferably 7: 1' although mole 1 ratio ofketone' to metal is from 121 up to 10:1 may be used.

Prior to cyclization, in the event that X is OH, the ketone must behalogenated with thionyl chloride or any other suitable halogenatingagent, for example, thionyl chloride-pyridine complex,'phosphorous-tri-chloride, phosphorous-tri-bromide, aqueous HCl oraqueous HBr. The halogenation reactionmay be carried out in the presenceor in the absence of an inert solvent such as benzene, toluene,cyclohexane or pyridine. The reaction temperature may range. from 20C upto 100C with a reaction temperature of C being preferred. The mole ratioof halogenating agentzketone of 3:1 is preferred when using thionylchloride and'a ratio of 1051 is preferred when using aqueous HCl andHBr.

The initial reaction may utilize, for-example, the following reactants:a (a) Acetyle'nic compounds:

3-Methylpent-4-yn-l-ol 3-Methylpent-4-ynl -chlor ide 3-Methylpent-4-ynl-bromide Pent-4-yn-l-ol Pent-4-ynl -chloride Pent4-yn-l -bromide (b)Cyclohexadienone compounds:

2,6,6-Trimethylcyclohexadien}l-one 2,3,4,5',6,6-Hexamethylcyclohexadien-l -one2,3,4,6,6-Pentamethylcyclohexadien-l-one 6,6-Dimethylcyclohexadien-l-one4,5,6,6-Tetramethylcyclohexadien-l-one2,4,5,6,6-Pentamethylcyclohexadien-l-one When the final cyclizationreaction is completed, the reaction mixture is worked-up using routinepurification procedures including the unit operations of extraction,crystallization, drying and/or distillation.

The individual tricyclic compounds of our invention can be obtained inpur-er form or in substantially pure form by conventional purificationtechniques. Thus, the products can be purified and/or isolated bydistillation, extraction, crystallization, preparative chromatographictechniques, and the like. lt has been found desirable to purify thetricyclic compounds by fractional distillation by vacuum.

It will be appreciated from the present disclosure that the tricycliccompounds and mixtures thereof according to the present invention can beused to alter, vary, fortify, modify, enhance or otherwise improve theflavor of a wide variety of materials which are ingested, consumed, orotherwise organoleptically sensed.

The term alter in its variousforrnswill be understood herein to mean thesupplying or imparting of a flavor character or note to an otherwisebland relatively tasteless substance, or augmenting an existing fla vorcharacteristic where the natural flavor is deficient in some regard orsupplementing the existing flavor impression to modify the organolepticcharacter.

Such compounds are accordingly useful in flavoring compositions. Aflavoring composition is taken to mean one which contributes apart ofthe overall flavor impression by supplementing or fortifying a naturalor artificial flavor in a material or onewhich supplies substantiallyall the flavor and/or aroma character to aconsumable article The termfootstuff as used herein includes both solid'and liquid ingestiblematerials for man or animals, which'materials usually do, butneednot,have nutritional value. Thus, foodstuffs includes meats, gravies, soups,convenience foods, malt, alcoholic, and other beverages, milk and dairyproducts, seafoods including fish, crustaceans, mollusks, and, the like,candies, vegetables, cereals, soft drinks, snacks, dog and cat food.other veterinary products, and the like.

The term tobacco will be understood herein to mean natural products suchas, for example, burley, Turkish tobacco, Maryland tobacco, flue-curedtobacco and the like including tobacco-like or tobaccobased productssuch as reconstituted or. homogenized leaf and the like, as well astobacco substitutes intended to replace natural tobacco, such as lettuceand cabbage leaves and the like. The tobaccos and, tobacco productsinclude those designed or used for smoking such as in cigarette, cigar,and pipe tobacco, as well as products such as snuff, chewing tobacco,and the like..

When the tricyclic compounds of this invention are used in a flavoringcomposition, they can be combined with conventional flavoring materials,or adjuvants. Such co-ingredients or flavoring adjuvants are well knownin the art for such use and have been extensively described in theliterature. Apart from the requirement that any such adjuvant materialbe ingestibly acceptable, and thus non-toxic or otherwisenon-deleterious,

conventional materials can be used and broadly include other flavormaterials, vehicles. stabilizers. thickeners, surface active agents,conditioners, and flavor intensifiers.

Such conventional flavoring materials include saturated fatty acids,unsatur ated fatty acids and amino acids; alcohols, including primaryand secondary alcohols; esters; carbonyl compounds including ketones andaldehydes; lactones; other, cyclic organic materials including benzenederivatives, a licyclic compounds, heterocyclics such as furans,pyridines, pyrazines and the like; sulfur-containing materials includingthiols, sulfides, disulfides and the like; proteins; lipids,carbohydrates; so-called flavor potentiators such as monosodiumglutamate, guanylates, and inosinates; natural flavoring materials suchas cocoa, vanilla, and caramel; essential oils and extracts such asanise oil; clove oil; and the like; and artificial flavoring materialssuch as vanillin; and the like.

Specific flavor adjuvantsare as follows:

Ethyl-2-methyl butyrate;

Vanillin;

Butyl valerate;

2,3-Diethyl pyrazine;

Methyl cyclopentenolone;

Benzaldehyde; v Valerian oil Indian; and

Propylene glycol ,The tricyclic compounds of our invention can be usedto contribute warm, patchouli-like aromas. As olfactory agents thetricyclic compounds of this invention canbe formulated into or used ascomponents of a perfume'composition. I

The term perfume composition is used herein to mean a mixture of organiccompounds, including, for example, alcohols, aldehydes, ketones,nitriles, esters, and frequently hydrocarbons which are admixed so thatthe combined odors of the individual components produce a pleasant ordesired fragrance. Such perfume compositions usually contain: (a) themain note of the bouquet or foundation-stone of the composition; (b)modifiers which round-off and accompany the main note; (c)-fixativeswhich include odorous substances which lend a particular note to theperfume throughout all stages of evaporation, and substances whichretard evaporation; and (d) top-noteswhich are usually lowboiling freshsmelling materials.

ln perfume compositions the individual component will contribute itsparticular olfactory characteristics, but the overall effect of theperfume composition will be the sum of the effect of each ingredient.Thus, the individual compounds of this invention, or mixtures thereof,can be used to alter the aroma characteristics of a perfumecomposition,for example, by highlighting or moderating the olfactory reactioncontributed by another ingredient in the composition.-

, The amount of the tricyclic compounds of this inventionwhich will beeffective in perfume compositions dependson many factors, includingtheother ingredients, their amounts and the effects which are desired. Ithas been found that perfume compositions containing -as.little as2percent ofthe tricyclic compounds of this'invention, or even less, canbe used to impart a patchouliscent to soaps, cosmetics, and the otherproducts. The amount employed can range up to 50 percent or higher andwill depend on considerations of cost, na-

ture of the end product. the effect desired on the fin ished product andparticular fragrance sought. 7

The tricyclic compounds of this invention can be used alone or in aperfume composition as an olfactory component in detergents and soaps,space odorants and deodorants; perfumes; colognes; toilet waters;.bathsalts; hair preparations such as lacquers, brilliantines, pomades. andshampoos; cosmetic preparations'such as creams, deodorants. handlotions, and sun screens; powders such as talcs, dusting powders, facepowder, and the like. When used as an olfactory component of a perfumedarticle, as little .as 0.01 percent of one or more of the tricycliccompounds will suffice to impart a warm patchouli aroma. Generally, nomore than 0.5 percent is required. a V

In addition, the perfume composition can contain a vehicle or carrierfor the tricyclic compounds 'alone or with other ingredients. Thevehicle can be a liquid such as an alcohol such as ethanol, a glycolsuch as propylene glycol, or the like. The carrier can be an absorbentsolid such as a gum or components for encapsulating the composition.

The following examples are given to illustrate em bodiments of theinvention as it is presently preferred to practice it. It will beunderstood that these examples are illustrative, and the invention isnot to be considered as restricted thereto except as indicated in theappended claims.

EXAMPLE I PREPARATION OF 3,3-DIMETHYL-6-( 3-CHLOROPROPYLBlCYCLO-[2.2.2]OCTA-5 ,7-DlENE-2-ONE Into an autoclave, 28 gm. of6,6-dimethyl cyclohexadiene-l-one, 28 gm. of 5-chloro-l-pentyne and 300ml of benzene are added. The autoclave is sealed and the reaction massis heated to 220C. The reaction is carried out over a period of 4 hoursafter which time the reaction mass is cooled to 20C. The reaction massis then removed from the autoclave and the resultant product is strippedof benzene and distilled at a vapor temperature of 136-138C and 3.0-3.2mm. Hg. pressure. The structure of the resultant product is confirmed byNMR, IR and mass spectral analyses to be 3,-3-dimethyl-6-(3-chloropropy1)-bicyclo-[2.2.2]-octa- 5,7-diene-2-one.

EXAMPLE II PREPARATION OF 3,3-DlMETHYL-6-( 3-CHLOROPROPYL)-BIC Y-CLO-[2.2.2]-OCTAN2-ONE Into an autoclave are placed 20 gm. of3,3-dimethyl- 6-(3-chloropropyl)-bicyc1o-[2.2.2']-octa-5,7-diene- 2-oneproduced by the process of Example 1 and, in addition, 300 ml ethylalcohol and 1 gm. of palladiumcarbon catalyst. The autoclave is sealedand then charged with hydrogen at a pressure of 200 pounds per squareinch. The reaction mass is stirred for a period of 5 hours at atemperature of 1001 15C during which period the pressure in theautoclave varies from 2 40 up to 260 pounds per square inch. Theautoclaveis then cooled and the product is removed and distilled. Twoproducts are obtained. The first has a boiling point of 90l C at 1.5 mm.Hg. pressure andis shown by IR, MS and NMR to be3,3-dimethyl-6-pr0pyl-bicyclo- [2.2.21-octane--one. The second is thedesired mate'- rials are placed: I I v Sodiu'm spheres 1.5 gmsTetrahydrofuran v 50.0 ml 3.3-'dimethy1-6-(3-chloropropyl)- 1.4 m.

The reaction mass is refluxed for a period of 4 hours and allowed tostand overnight. The liquidphase is's'eparated from the sodium spheres.The liquid phase is then washed with I IOO m] water-and acidifiediwithdilute hydrochloric acid. The resultant material ex tractedltwice withdiethyl ether. The combined ether phases are washed withsaturatedaqueous NaHCOg and then dried over anhydrous magnesium sUlfa'teThesolution is stripped of sovent and the remainingresidue is separated'ona GLC column: g,

- (1/8 inch'X 41,20. percent SE-30 (a methyl silicone oil availablefrom; Analabs, Inc,,of P.0. 501,.Nbrth Ha ven, Connecticut06473); 100-220c 8C/rnin.).1

The structure. of the major product of the reaction (43 percent by GLC)was shown to be thetitlematerial.

Mass spectral analysis is as follows: 41,55, 84, 9 7,

l33,and l 1 0. t NMR analysis is as fol1ows: l .O6(s,'61-1), complexsig-. nals from 1.0 to 2.1 ppm.

EXAMPLE iv PREPARATION OF 1,3,3-TRlMETHYL-6-( 1-METHYL-3-HYDROXYPROPYL)-BlCYCLO-[2.2.2]-OCTA-5 ,7-

'- D1EN-2-ONE A solution of 27.2 gm. (0.20 ml) of 2,6,6-trimethylcyclohexadien-l-one and 28,gm.,(0.28 ml) of3-methylpent-4-yn-l-ol in 300 cc of benzene is placed in a 2 literstirred autoclave and heated to 2200C for 5 hours. At the end of thistime, GLC shows no trimethylcyclohexadien-l-one remaining and thesolvent is removed under vacuum and the residue is distilled to yieldabout 37 gm. of the product, 1,3,- 3-trimethyl-6-(1-methyl-3-hydroxypropyl )-bicyclo- [2.2.2]-0cta-5,7-dien-2-one.

EXAMPLE V PREPARATION OF 1,3,3-TR1METHYL-6-( l'-METHYL-3- HYDROXYPROPYL)-BICYCLO-[ 2.2.2]-OCTAN- 2-ONE Into a stirred autoclave, 30 gm. (0.13ml) of 1,3,3- trimethyl-6-( 1-methyl-3-hydroxypropyl)-bicyclo-[2.2.2]-octa-5,7 dien-2-one, 0.5 gm. of 5 percent of palladium-carbonand 300 ml of isopropyl alcohol is added. The autoclave is pressurizedto 400 pounds per square inch with hydrogen and heated to C for 6 hours.At the end of this time, the mixture is filtered,

stripped of solvent and vaccum distilled, yielding about 27 gm. (90%) ofthe product. 1.3.3-trimethyl-6-(1-methyl-3-hydroxypropyl)-bicyclo-[2.2.2]-octan-2-one.

EXAMPLE V1 PREPARATION OF 1,3 ,3-TRlMETHYL-6-( l-METHYL-3- CHLOROPROPYL)BlCYCLO-[ 2. 2.2]-OCTAN- 2-ONE EXAMPLE V11 PREPARATION OF PATCHOULIALCOHOL A sodium sand is prepared by heating 1 1.5 gm. of sodium inxylene and stirring. The xylene is decanted and replaced by 300 cc ofanhydrous tetrahydrofuran. A solution of 20 gm. (0.078 mole) of1,3,3-trimethyl-6- l-methyl-3-chloropropyl )-bicyclo-[ 2.2.2]-octan-2-one in 50 cc of tetrahydrofuran is added with stirring at roomtemperature over a 15 minute period. A slight exotherm occurred duringaddition. The solution is brought to reflux and held there for 3 hours.At the end of this time, the solution is decanted from the excess sodiumand is acidified with 5 percent l-ICl. The excess acid is neutralized bya single wash with saturated sodium bicarbonate solution. The solutionis dried over magnesium sulfate, filtered and stripped, yielding aresidue which is recrystallized from hexane to yield about 10 gm. (50%)of racemic patchouli alcohol, mp 3940 having the structure:

EXAMPLE VIII Perfume Formulation The following woody cologne" perfumeformulation is prepared:

4-(4-methyl-4-hydroxy amyl) A cyclohexene carboxaldehyde 40 Ylang 2'Petitgrain Paraguay Gamma methyl iono'ne3a-Methyl-d0decahydr0-6.6,9atrimethylnaphtho-(2,l-h) furan 5 Productproduced by reaction of acetic Ingredients -Continued Parts by Weightanhydride. polyphosphoric acid and 1,5.9-trimethyl cyclododecatriene-l.59

according to the process of Example I of U.S. Patent 3.718.697 5Octahydro-9.9-dimethyl-1.fi-methanonaphthalene-1-(21-l)-ol producedaccording to Example ll 15Octahydro-9,9-dimethyl-1,-methanonaphthalene-l- (2l-l)-ol imparts a warmpatchouli-like character to this woody cologne composition.

' EXAMPLE 1X Preparation of a Soap Composition A total of gm. of soapchips produced from unperfumed sodium base toilet soap made from tallowand coconut oil are mixed with 1 gm. of the perfume composition setforth in Example V111 until a substantially homogeneous composition isobtained. The soap composition manifests a characteristic woody colognearoma having a warm patchouli-like character.

EXAMPLE X Preparation of a Soap Composition A total of 100 gm. of soapchips produced from unperfumed sodium base toilet soap made from tallowand coconut oil is mixed with 1 gm. of octahydro-9,9-dimethyl-l-methanonaphthalene 1-(2H)-o1 until a substantiallyhomogeneous composition is obtained. The soap composition manifests awarm patchouli-like character.

EXAMPLE X1 Preparation of a Detergent Composition A total of 100 gm. ofa detergent powder sold under the trademark RINSO are mixed with 0.15gm. of a perfume composition containing the mixture obtained in ExampleV111 until a substantially homogeneous composition having a woodycologne fragrance with a warm patchouli-like character is obtained.

EXAMPLE XII Preparation of a Cosmetic Base EXAMPLE X111 Liquid DetergentContaining Octahydro-9,9-Dimethyl-1,6-Methanonaphthalene-l- (2H )-OlConcentrated liquid detergents with a patchouli-like odor containing 0.2percent, 0.5 percent and 1.2 percent of the product produced inaccordance with the process of Example 111, octahydro-9,9-dimethyl-l,6-

EXAMPLE'XIV Preparation of Cologne and Handkerchief Perfume Thecomposition of Example VIII is incorporated in a cologne having aconcentration of 2.5 percent in 85 percent aqueous ethanol; and into ahandkerchief perfume in a concentration of 20 percent (in 95 percentethanol). The use of the composition of Example VIII affords a distinctand definite woody cologne aroma having a warm atchouli-like characterto the handkerchief perfume and to the cologne.

EXAMPLE XV Cologne and Handkerchief Perfume I Theoctahydro-9,9-dimethyll ,6-methanonaphthalene-l-(2H)-ol produced by theprocess of Example 111.

is incorporated into a cologne having" a concentration of 2.5 percent in85 percent ethanol; and into a handkerchief perfume in a concentrationof percent (in 95 percent ethanol); The'octahydro-9,9-dimethyl-l ,6-methanonaphthalene-l-(2I-I)-ol' produced in Example III affords adistinct and definite warm patchouli-like aroma to the handkerchiefperfume and to the cologne.

EXAMPLE XVI 7 Flavor Composition The following basic walnut flavorformulation is prepared:

I Parts by Weight Ingredients Ethyl-Z-Methyl Butyrate 10 Vanillin 40Butyl Valerate 40 2,3-Diethyl Pyrazine v 5 Methyl Cyclopentenolone 80Benzaldehyde 60 Valerian Oil Indian 0.5

(1% in 95% aqueous ethanol alcohol) Propylene Glyc'ol 764.5

Octahydro-9,9-dimethyl- 1 ,6-methanonaphthalenel- (2H)-ol produced bythe process of Example 111 is added to the above formulation at the rateof 1.5 percent. This formulation is compared toga formulation which doesnot have octahydro-9,9-dimethyl-l ,6- methanonaphthalene-l-(2H)-ol addedto it, at the rate of ppm in water. The formulation containingoctahydro-9,9-dimethyll ,6-methanonaphthalenel 2H )-01 has awoody-balsamic, fresh walnut kernel and walnut skin-like taste and, inaddition, has a.fuller mouthfeel and longer lasting taste. The flavorthat has added to it,octahydro-9.9-dimethyl-1,o-methanonaphthalene-1-(2H)-ol, is preferred bya group of flavor panelists, and they consider it to be a substantiallyimproved walnut flavor.

EXAMPLE XVII Beverage The addition of octahydr'o-9,9-dimethyl-l,6-

methanonaphthalene-l-(2H)-ol prepared by the process of Example 111 attherate of 0.3 ppm to a commercial Cola beverage gives the beverage afuller woodybalsamic long lasting taste and adds to the pleasant topnotes of the beverage. When comparing the Cola beverage containingoctahydro-9.9-.dimethyl-l ,6- methanonaphthalene-l-(2H)-ol to onehavingthe same .formula but not containingoctahydro-9.9-dimethyll,o-methanonaphthalene-l(2H)-ol. a five memberbranch panel prefers the beverage containing the octahydro-9,9-dimethyll ,6-methanonaphthalene- 1 2H EXAMPLE xvm Tobacco FlavorFormulation Cigarettes'are produced using the following tobaccoformulation:

Ingredients Parts by Weight Bright 40.1 Burley 24.9 Maryland l.l Turkish1 1.6 Stem (flue-cured) 14.2 Glycerine 2.8

At the rate of 0.2. percent, thefollowing tobacco flavor formulation isapplied to all of the cigarettes produced with the above tobaccoformulation.

To 50 percent of the cigarettes, 10 and 20 ppm ofoctahydro-9,9-dimethyl-l ,6-methan'onaphthalenel (2H)-ol are added.These cigarettes are hereinafter called experimental cigarettes and thecigarettes without the octahydro-9,9-dimethyl-1,6-methanonaphthalene-l-(2H)-ol are hereinafter called control cigarettes.The control and experimental cigarettes are then evaluated by pairedcomparison and the results are as follows:

a. In aroma, the experimental cigarettes are found to be more aromatic.

b. In smoke flavor, the experimental cigarettes are found to be morearomatic, more sweet, more bitter, more green, richer and slightly lessharsh in the mouth and more cigarette tobacco-like than the controlcigarettes.

The experimental cigarettes containing 20 ppm ofoctahydro-9,9-dimethyl-1,6-methanonaphthalene-1- (2H)-ol are found to-bewoody, slightly chemicaland mouth-coating in the smoke flavor.

All cigarettes both control and experimental, are evaluated for a smokeflavor with 20 mm cellulose ac'etate filter. Octahydro-9,9-dimethyl-l,6- methanonaphthalene-l-(2H)-ol enhances the tobaccolike taste of theblended cigarette.

Ingredients Parts by Wcight 2.2.3.4.5 .6-Hexamethyl-Cyclohcxa-3.5-dien-I -one '4-Pcntyn- 1 -ol Benzene 29.7 gm. 300.0 ml

The reaction mass is stirred after the autoclave is sealed for a periodof 2 /2 hours at 215-220C. After standing overnight, an additional of7.5 gm. of 4- pentyn-l-ol is added and the mixture is again stirredat220C for an additional 2 hours. The mixture is then removed from theautoclave and stripped of solvent yielding 94.1 gm. of a highlyviscousmaterial. This highly viscous material is distilled through amicrovigreaux rushover column at approximately 1.0 mm. Hg. pressure,yielding 50.8 gm. of the title material, 1,- 3,3,4,7,8-hexamethyl-6-(3-hydroxypropyl)-bicyclo- (2.2.2 )-octa-5,7-dien-2-one,which was 89.8 percent by GLC. I

Mass spectral analysis 41, 147, 247 Infra-red analysis gives acharacteristic peak at 1702- NMR Analysis is as follows: 0.92(s,3H),0.95(s,3l-l), l.40(s,6H). l.66(s,3l-i), l.76(s,3H), 2.lO(m,2H),3,64(t,2H), 5.72(m,lH) ppm.

EXAMPLE XX Preparation of v l,3,3,4,7,8-Hexamethyl-6-(3-Hydroxypropyl)-Bicyclo- (2.2.2)-Oct-7-En-2-One Intoia 2 literautoclave, the following ingredients are placed:

is as follows: m/e 178, 191,

Ingredients Parts by Weight l,3,3.4,7,8-hexamethyl-6-(3-hydroxypropyl)bicyclo-(2.2.2)-octa-5,7-

dien-Z-one 5'71 Palladium on carbon lsopropyl alcohol 1 gm 300 ml.

EXAMPLE XXI Preparation of v l,3,3.4.7.8Hexamethyl-6-( 3-Chloropropyl)Bicyclo- (2.2.2-)-Oct-7-En-2-One Into a 250 ml three-neck flaskequipped with dropping funnel. nitrogen inlettube, thermometer andreflux condenser, the following materials are placed:

ingredients vParts by Weight Pyridine i v H5l3,3.4.7.8-hexamethyl-6-(3-hydroxy 'l3.0 gm.

16.0 gm. of thionyl chloride is added dropwisewith stirring to 'thereaction mass over a period of 25 min-. utes. During this time, thereaction mass temperature rises rapidly and is controlled by the use ofan ice bath so as not to exceed 50C. After the addition of the thionylchloride is completed, 5.8 gm. of pyridine and then an additional 8.0gm. of thionyl chloride is added while maintaining the temperature ofthe reaction mass at 40C. The reaction mass is then stirred for a periodof 3 hours at room temperature and is then extracted with seven 40mlportions-of diethyl ether; The combined ether extracts arethen strippedon a rotary "evaporator. The resulting residue'is washed with mlofwaterf Methylene chloride is added to facilitate separation of theresulting aqueous and organic layers. The water wash is back-extractedwith methylene chloride and the combined methylene chloride phases arewashed over once more with water and then'drie'd and stripped. Theresulting residue weighs 27.4 gm. Mass spectral and IR analyses yieldinformation that the resulting product is the title compound.

Mass spectral analysis is as follows: m/e 135, 178,

41, 212 282 (Parent peak) EXAMPLE XXII Preparation of g IHexahydrohexamethylmethanonaphthalenol Into a 250 ml three neck flaskequipped with stirrer,

Ingredients Parts by Weight Sodium sand produced by vigorously. 2.2-.gm.shaking sodium spheres in hot xylene Tetrahydrofuran Y i w 75.0 mll.3.3.4,7.8-hexamethyI-6-(3-chloropropyl) 2.0 gm.

bicyclo-(2.2.2)-oct-7-cn-2-one The reaction mass is stirred atrefl'uxfor a period of 30 minutes. After the 30 minute period, thesodium sand coagulates into one lump. Stirring is continued at refluxfor a period of 3 additional hours. The mixture is then cooled and theliquid is decanted from the sodium. The reaction product is'then addedto 100 ml of water and the mixture is acidified to a pH of 3 with 5percent hydrochloric acid. 5 0 ml of diethyl ether is then added and thelayers are then separated. The

aqueous layer is extracted once with 50 ml of diethyl .ether. The etherlayers are combined and are washed (i) with water, followed by (ii)saturated sodium bicar- EXAMPLE XXIII Preparation of 1,3,3-Trimethyl-6-( 3 -Hydroxypropyl ).-Bicyclo-( 2.2.2

Octa- ,7-Dien-2-One Y Into a 2 liter autoclave, the followingingredients are added:

Ingredients Parts by Weight 2,2.6-Trimethyl cyclohexadienone 25.0 gm.4-Pentyn-1-ol 25.0 gm. Benzene 300.0 ml

The autoclave is sealed and the reaction mass is stirred for a period of12 /2 hours at220C. The reaction mass is then removed from the autoclaveand stripped of solvent on a rotary evaporator. A GLC sample of thematerial shows no 2,2,6-trimethylcyclohexadienone remaining (As inch X10 percent carbowax; 80-220C at 8C/min.). The residue (58.1 gm.) is rushdistilled on a micro vigreaux column under vacuum, yielding 29.8 gm. ofa product of boiling point 150C at 1.5 mm. Hg. pressure Mass spectral,IR and NMR analyses yield the information that the product is the titlecompound.

Mass spectral analysis is asfollows: m/e 70, 105,

106, 42, 117, 91 Infra-red analysis shows a characteristic peak at 1709NMR analysis is as follows: l.06(s,6H), 1.45(s,3H), 1.70(m,2H),2.17(m,2H), 3.40(m,1H), 3.62(t,2H), 6.05(m,2H), 6.53(t,lH)

EXAMPLE XXIV Preparation of l,3,3-Trimethyl-6-( 3-Hydroxypropyl)-Bicyclo-( 2.2.2 Octan-Z-One Into a two liter autoclave. the followingingredients are added:

Ingredients Parts by Weight 57! Platinum on carbon. prcreduced 0.5 gm.l.3.3-trimethyl-6-( 3-hydroxypropyl 2 7.8 gm.hicyclu-(2.2.2)octa-5.7-dien-2-one 7 Isopropyl alcohol The autoclave issealed and pressurized to pounds per square inch with hydrogen. Thereaction mass is heated to C and the pressure rises to 220 pounds persquare inch. Heating and stirring is continued until GLC or massspectral analyses indicates reaction is complete (about 20 hours). Theautoclave is vented and the reaction mass is filtered stripped ofsolvent, yielding 25.4 gm. of residue. Djst'llation under vacuum gave a50 percent yield of th tlematerial, boiling point l4Sf l50C at l.5,m m.'pressure.

Mass spectral, IR and NMR analyses confirm the postulated structure. I

EXAMPLE XXV Ingredients Parts by Weight l.3,3-Trimethyl-6-(B-hydroxypropylI- 13.8 gm. bicyclo-(2.2.2)-octan-2-one Benzene 6.0 ml.

14 gm. of thionyl chloride is added to the reaction: mass over a periodof 5 minutes-with stirring, the addi tion causing an exothermicreaction. The reaction mass temperature rises to 55C. Followingaddition, the mixture is stirred for 3 hours at reflux. The pottemperature is initially 92C at reflux, but rises to 100C after-a period of 3 hours.

After cooling, the mixture is poured onto '100 gm. of ice. The resultingice mixture is then allowed to warm I to room temperature and isthenf'neutralized withisodium bicarbonate and the reaction mass-icemixture is extracted 4 times with diethyl ether. The combined etherextracts are dried over anhydrous magnesium sulfate and filtered. Theether is then stripped on a rotary evaporator yielding 14.4 gm. ofresidue. The residue is rush-distilled on a micro vigreaux column at atemperature of 143l44C at a pressure of 1.2 mm. Hg. Mass spectral, IRand NMR analyses yield the data that the product is the title compound.

Mass spectral analysis is as follows: m/e 82, 170,

171, 41, 242 (Parent peak) NMR analysis is as follows: 0.91(s,3H),1.07(s,3H), 1.1 1(s,3H), 1.4-2.1 (signal for 12H), 3.47(t,2H) pp EXAMPLEXXVI Synthesis of Dihydronorpatchoulinol Into a 500 ml flask fitted witha condenser. stirrer. thermometer and nitrogen inlet tube, the followingma terials are placed:

ingredients Parts by Weight Xylene 15 ml Sodium 7.5 gm.

The mixture is heated to 90C while stirring vigorously. When the sodiumis completely dispersed in fine particles, the stirring is ceased andthe heat source is removed after which time the mixture is cooled usingan ice bath. When the sodium dispersion temperature reaches 30C, thexylene is decanted and replaced with 200 ml of tetrahydrofuran. Thesuspension is heated to reflux and l] gm. of 1,3,3-trimethyl-6-(3-chloropropyl)-bicyclo-[2.2.2]-octan-2-one are added. The reaction massis then maintained at reflux for a period of 3 hours with moderatestirring. The sodium remains dispersed untilS minutes before reflux isdiscontinued where upon it coagulates into a large ball. The heat sourceis then removed and stirring is ceased. The reaction mass is decantedfrom the sodium, acidified to a pH of 3 with 5 percent of hydrochloricacid and then neutralized to a pH 7 with a sodium bicarbonate solution.The organic layer is separated from the aqueous layer, and the aqueouslayer is extracted four times with 100 ml portions of diethyl ether andvacuum distilled at a temperature of 120C and a pressure of 0.6 mm. Hg.Mass spectral, IR and NMR analyses yield the data that the majorproduct, obtained in 64 percent yield, is the title compound having thestructure:

EXAMPLE XXV" Preparation of Octahydro-9,9-Dimethyll,6-methanonaphthalen- 1 (2H )-Ol into a 250 ml three neck flask underhelium and equipped with reflux condenser, stirrer, thermometer, andheating mantle, the following materials are placed:

Ingredients Parts by Weight Lithium wire containing l9: sodium 0.17 gm.Diethyl ether (anhydrous) 50.00 ml3,3-Dimethyl-6-(3-chloropropyl)bicyclo- 1.4 gm.

(2.2.2 )octan-2-one The reaction mass is stirred at reflux for a periodof 3 /2 hours. After standing overnight, an additional 50 ml of diethylether is added and then 50 ml of water. The ether layer is separated andthe water layer is extracted once with diethyl ether. The combined etherlayers are dried over anhydrous magnesium sulfate and stripped ofsolvent yielding an oil having two phases. This oil is redisolved indiethyl ether, redried over anhydrous magnesium sulfate and restrippedof solvent yielding 0.9 gm. ofoil. GLC 4; inch X l0, l0% carbowax. l00to 220C at 8C per minute), IR and mass spectral analyses yield theinformation that 22 percent of the reaction mass is the title materialhaving the structure:

2. The compound having the structure:

1. OCTAHYDRO-9,9-DIMETHYL-1,6-METHANONAPHTHALEN-1 (2H)OL HAVING THESTRUCTURE:
 2. The compound having the structure: